TABLE 4.

List and description of few pharmacogenomic (PGx) clinical implementation programs and initiatives.

Description	Choice of drug-gene pairs	Genotyping strategies and methods	Results, EHR integration and CDS	Education
PMP: PERSONALIZED MEDICINE PROGRAM at the University of Florida Health since 2012 [1-3] https://precisionmedicine.ufhealth.org/about-us/
➢ It builds and evaluates PGx information for clinical implementation	➢ Based on CPIC guidelines, genotyping of CYP2C19 for clopidogrel was initially launched, followed by TPMT for thiopurines IFNL3 for PEG-IFNα, CYP2D6 for opioids, CYP2D6 and CYP2C19 for SSRIs, and CYP2C19 for PPIs	➢ Involvement of the Pharmacy and Therapeutics Committee	➢ Hospital regulatory body leads the integration of relevant PGx results into EHR and CDS system	➢ Interactive learning opportunities focusing on review of evidence and development of clinical recommendations
➢ It also identifies and addresses common challenges		➢ Preemptive genotyping	➢ Rapid reporting of results into the EHR (Epic) after 2–3 days	➢ Education of target audience by provider group. Provision of material (printed and online) for clinicians and patients
	➢ Choice was also based on FDA product label, presence of no function genetic variants or common allele frequency, potential to prevent adverse drug events, available evidence supporting genotype-guided dosing recommendations, and physician request	➢ Life technologies Quant Studio Open Array technology. Chip-based genotyping	➢ Use of Best Practice Advisories (BPA) CDS system that provides interpretation and clinical recommendations based on patient’s genetic results	➢ Development of a novel elective course for pharmacy students
				➢ Development of accredited post-graduate training programs in PGx
				➢ Publication of a newsletter titled “SNP.its”
PG4KDS: PHARMACOGENETICS FOR KIDS at the St. Jude Children’s Research Hospital since 2011 [3-5] https://www.stjude.org/treatment/clinical-trials/pg4kds-pharmaceutical-science.html
➢ It targets children with cancer	➢ Based on CPIC guidelines, genotyping for CYP2C19, CYP2D6, TPMT, and SLCO1B1 were initially chosen coupled with 12 high-risk drugs. After that, DPYD, UGT1A1, CYP3A5, CYP2C9, NUD15, RYR1, mt-RNR1, CACNA1S, G6PD, and CYP2B6 were genotyped, which resulted in therapeutic guidance for 66 drugs	➢ Creation of a subcommittee of the hospital Pharmacy and Therapeutics Committee for PGx oversight	➢ Test results are first displayed in a specialty flow sheet tab. Some are then moved to the EHR with phenotype description, interpretation, and implication	➢ Development of accredited post-graduate programs in clinical PGx
➢ It preemptively analyzes patients’ DNA for a large number of gene variants, generates reports, and incorporates relevant PGx data in EHR coupled with CDS.	➢ Focus on drugs for children with cancer	➢ Launching of a research protocol with informed consent to implement preemptive genotyping strategy with integration into the EHR.	➢ Consultation notes are available for clinicians with basic PGx knowledge as a passive decision support tool	➢ Website includes presentations and publications on the implemented drug-gene pairs
		➢ Initially started with the Affymetrix DMET Plus assay, later moved to the right patient right drug (RPRD) diagnostic with the PharmacoScan array	➢ Results and consultations are available in the patient’s online portal
			➢ Active CDS alerts with relevant drug prescriptions
PREDICT: PHARMACOGENOMICS RESOURCE FOR ENHANCED DECISIONS IN CARE AND TREATMENT at Vanderbilt University Medical Center since 2010 [3, 5, 6]
https://www.vumc.org/predict-pdx/
➢ It chooses drug-gene pairs, genotypes, filters, interprets, and incorporates PGx data and CDS in EHRs to be accessible for healthcare providers in routine care	➢ Based on CPIC guidelines, CYP2C19 was initially genotyped for clopidogrel followed by CYP2C9 and VKORC1 for warfarin therapy	➢ Involvement of the Pharmacy and Therapeutics Committee	➢ Results are entered by laboratory staff to the laboratory information system (Cerner Millennium Helix® module)	➢ Development of “My Drug Genome” website
	➢ Focus on drugs for cardiovascular diseases	➢ Preemptive genotyping	➢ Results of discrete variants are found on the EHR (Epic) as patient friendly version through My Health At Vanderbilt (MHAV)	➢ Support for the development of a Massive Open Online Course (MOOC) on PGx
		➢ TaqMan® chemistry-based platforms such as Oper QuantStudio™ 12K Flex Real-Time OpenArray Polymerase Chain Reaction (PCR) platform for more than 50 samples/day	➢ Application of end-to-end CDS system to help in interpretation of results and guidance in medication/dose selection	➢ Offering of a post-doctoral fellowship program and training in pharmacogenomics
			➢ Use of drug-gene interaction knowledge to interpret genotype-phenotype relation and linking of a specific CDS to a specific genetic result
RIGHT: RIGHT DRUG, RIGHT DOSE, RIGHT TIME at the Mayo Clinic since 2013 [3, 5, 7]
https://www.mayo.edu/research/centers-programs/center-individualized-medicine/research/clinical-studies/right-10k
➢ It evaluates available PGx studies and guidelines	➢ Based on CPIC guidelines, genotyping of SLCO1B1 for simvastatin was initially done followed by CYP2C19 for clopidogrel, IFNL2 for interferon, CYP2D6 for tramadol, tamoxifen and codeine, HLA-B*1,502 for carbamazepine and abacavir, and TPMT for thiopurines	➢ Involvement of the pharmaceutical formulary committee in approving drug-gene pairs and incorporation of results with CDS.	➢ Storage of molecular diagnostic laboratory results in EHR.	➢ The CDS rules provide information on drug-gene pair at point of care as a “Just in Time” support system
➢ It genotypes and incorporates PGx data and CDS into EHR to be accessible for healthcare providers	➢ Choice was also based on commonly prescribed drugs containing actionable PGx variants, FDA list of PGx biomarkers, PharmGKB list of genes and drugs, Indiana University Drug Interactions website, articles published on the subject of PGx, and current PGx tests offered by the Mayo Clinic’s Department of Laboratory Medicine and Pathology	➢ PGx implementation model following this sequence: Institutional leadership support, Pharmacogenomics governance, Clinical approval, Laboratory results, Pharmacogenomics education, Pharmacogenomics knowledge, CDS-EHR implementation, and long-term maintenance	➢ Development and maintenance of CDS rules that involve conversion of variants to standard notation and interpretation, workflow analysis, and data mapping	➢ Information and interpretation of PGx testing is available for patients through “Online Patient Services account”
		➢ Development of Mayo Clinic Biobank Community Advisory Board (CAB) for recruitment and consenting patients	➢ CDS rules are implemented for interpreting results, prescribing decisions, and providing actionable alert messages	➢ Development of “Ask Mayo Expert” for patient education
		➢ Preemptive research genotyping through the RIGHT protocol	➢ Active CDS alerts are developed in the computerized physician order entry (CPOE) applications	➢ Establishment of grand rounds, presentations, online modules, videos, brochures, and links to results through the patient’s portal
		➢ Use of PGRN-Seq technique		➢ Offering of a post-doctoral fellowship program and training in PGx
The 1200 PATIENT PROJECT at the University of Chicago Center for Personalized Therapeutics since 2011 [3, 5, 8]https://cpt.uchicago.edu/1200-patients-project/
➢ It assesses the effectiveness and feasibility of applying preemptive PGx testing in clinical settings	➢ Large number of germline polymorphisms for outpatient medical care	➢ Research study targeting 1,200 patients for the implementation of preemptive genotyping with informed consent	➢ Results, interpretation and education are available through research web-portal or genomic prescribing system (GPS)	➢ Development of “YourPGx Portal”
➢ It also evaluates the impact of using PGx results on prescription decisions and patients’ outcome	➢ Participants should be taking 1 to 6 prescription medications of interest	➢ Use of ‘ADME pharmacogenomics panel’ and custom Sequenom panel		➢ Offering of a post-doctoral fellowship program and training in PGx
	➢ Choice of genes based on published clinical evidence for their PGx role
U-PGx: UBIQUITOUS PHARMACOGENOMICS Consortium in Europe since 2016 (The Netherland, United Kingdom, Germany, Sweden, Austria, France, Italy, Spain, Greece, Slovenia) [3] https://uPGx.eu/
➢ It evaluates the cost-effectiveness and impact of preemptive PGx implementation in Europe on patient outcome by conducting ‘The Preemptive Pharmacogenomic testing for Prevention of adverse drug reactions (PREPARE)’ study	➢ Panel of 50 variants in 13 pharmacogenes that have actionable drug-gene interaction based on the Dutch Pharmacogenetics Working Group (DPWG) guidelines	➢ Research study (PREPARE) on the preemptive implementation of a panel of pharmacogenes covering several therapeutic areas	➢ Medication Safety Code system: “Safety-Code card” and Genetic Information Management Suite for physicians	➢ Established E-learning PGx programs for healthcare providers
	➢ The 13 genes evaluated are: CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, HLA‐ B*5701, SLCO1B1, TPMT, UGT1A1, VKORC1	➢ Use of SNPline platform
	➢ For patients being started on a drug of interest that has clinically relevant genetic interaction with the genes mentioned. The chosen drugs are very similar to the ones listed in Table 2

EHR, electronic health records; CDS, clinical decision support.

1. Johnson, J.A., et al., Institutional profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics. Pharmacogenomics, 2013. 14 (7): p. 723-6.

2. Cavallari, L.H., et al., Institutional profile: University of Florida Health Personalized Medicine Program. pharmacogenomics, 2017. 18 (5): p. 421-426.

3. Van der Wouden, C.H., et al., Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium. clin pharmacol ther, 2017. 101 (3): p. 341-358.

4. Haidar, C.E., et al., Advancing Pharmacogenomics from Single-Gene to Preemptive Testing. annu rev genomics hum genet, 2022. 23: p. 449-473.

5. Luzum, J.A., et al., The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems. clin pharmacol ther, 2017. 102 (3): p. 502-510.

6. Liu, M., et al., A Tutorial for Pharmacogenomics Implementation Through End-to-End Clinical Decision Support Based on Ten Years of Experience from PREDICT., clin pharmacol ther, 2021. 109 (1): p. 101-115.

7. Bielinski, S.J., et al., Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol. Mayo Clin Proc, 2014. 89 (1): p. 25-33.

8. O'Donnell, P.H., et al., The 1,200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics. Clin Pharmacol Ther, 2012. 92 (4): p. 446-9.